Localization of human SAA gene(s) to chromosome 11 and detection of DNA polymorphisms

Kluve‐Beckerman, Barbara; Naylor, Susan L.; Marshall, Angus; Gardner, Julia; Shows, Thomas B.; Benson, Merrill D.

doi:10.1016/0006-291x(86)90352-9

Cited by 49 publications

(11 citation statements)

References 20 publications

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“…The human SAA gene family is clustered within a 160 kb region of chromosome 11p15.1 (Kluve-Beckerman et al 1986; Sack et al 1989), a region analogous to the chromosome 7 region in the mouse (Taylor and Rowe 1984). Human Saa1 and Saa2 are acute phase genes.…”

Section: Saa Genes and Molecular Biologymentioning

confidence: 99%

Serum amyloid A – a review

Sack

2018

Mol Med

370

350

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Serum amyloid A (SAA) proteins were isolated and named over 50 years ago. They are small (104 amino acids) and have a striking relationship to the acute phase response with serum levels rising as much as 1000-fold in 24 hours. SAA proteins are encoded in a family of closely-related genes and have been remarkably conserved throughout vertebrate evolution. Amino-terminal fragments of SAA can form highly organized, insoluble fibrils that accumulate in “secondary” amyloid disease. Despite their evolutionary preservation and dynamic synthesis pattern SAA proteins have lacked well-defined physiologic roles. However, considering an array of many, often unrelated, reports now permits a more coordinated perspective. Protein studies have elucidated basic SAA structure and fibril formation. Appreciating SAA’s lipophilicity helps relate it to lipid transport and metabolism as well as atherosclerosis. SAA’s function as a cytokine-like protein has become recognized in cell-cell communication as well as feedback in inflammatory, immunologic, neoplastic and protective pathways. SAA likely has a critical role in control and possibly propagation of the primordial acute phase response. Appreciating the many cellular and molecular interactions for SAA suggests possibilities for improved understanding of pathophysiology as well as treatment and disease prevention.

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Section: Saa Genes and Molecular Biologymentioning

confidence: 99%

Serum amyloid A – a review

Sack

2018

Mol Med

370

350

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“…This is a serious complication of chronic or recurrent inflammatory conditions, e.g., juvenile chronic arthritis, in which persistently high serum levels of SAA are found. More than one human SAA gene exist (16,25,41), and in mice three active SAA genes and a pseudogene have been described (29,51). Both human and murine SAA gene expression can be induced by the cytokines interleukin-1 (IL-1) and tumor necrosis factor (39,49 (42).…”

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confidence: 99%

Identification of cis-acting sequences responsible for phorbol ester induction of human serum amyloid A gene expression via a nuclear factor kappaB-like transcription factor.

Edbrooke¹,

Burt²,

Cheshire³

et al. 1989

Mol. Cell. Biol.

131

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We have analyzed the 5'-flanking region of one of the genes coding for the human acute-phase protein, serum amyloid A (SAA). We found that SAA mRNA could be increased fivefold in transfected cells by treatment with phorbol 12-myristate 13-acetate (PMA). To analyze this observation further, we placed a 265-base-pair 5' SAA fragment upstream of the reporter chloramphenicol acetyltransferase (CAT) gene and transfected this construct into HeLa cells. PMA treatment of these transient transfectants resulted in increased CAT expression. Nuclear proteins from PMA-treated HeLa cells bound to this DNA fragment, and methylation interference analysis showed that the binding was specific to the sequence GGGACTTTCC (between -82 and -91), a sequence previously described by R. Sen and D. Baltimore (Cell 46:705-716, 1986) Human serum amyloid A (SAA) is a major acute-phase reactant produced mainly by the liver. During periods of inflammation and tissue damage, serum levels of SAA can increase by up to 1,000-fold. SAA is also the precursor peptide of the amyloid A protein subunit of amyloid fibrils in secondary, or reactive, amyloidosis (24). Insoluble fibrils are deposited extracellularly in multiple organs, compromising their normal function. This is a serious complication of chronic or recurrent inflammatory conditions, e.g., juvenile chronic arthritis, in which persistently high serum levels of SAA are found. More than one human SAA gene exist (16,25,41), and in mice three active SAA genes and a pseudogene have been described (29,51). Both human and murine SAA gene expression can be induced by the cytokines interleukin-1 (IL-1) and tumor necrosis factor (39,49 (42). DNA fragments from the 5'-flanking region of the SAA genomic clone, SAAg9 (49), were subcloned into M13mpl8 and -mpl9 and sequenced by using sequence-specific oligonucleotides generated on an Applied Biosystems automated nucleotide synthesizer.Plasmid-constructions. A 265-base-pair (bp) Sau3A DNA fragment, from the promoter region and 33 bp of the first exon of the human SAA gene, was cloned between the BglII-BamHI sites of the vector, pTK.CAT3 (31). This construct contains the entire CAT gene, and the thymidine kinase promoter has been replaced with the SAA 5'-flanking region. As a control, the thymidine kinase promoter was deleted from pTK.CAT3 with BglII-BamHI. The subsequent constructs, OCAT/265 and OCAT, were used to study PMA inducibility conferred on the CAT gene by the SAA promoter region.The 265-bp promoter fragment was also cloned into the BamHI site of the vector pBluescriptSK, generating plasmid 9-2. This vector contains both T3 and T7 promoters flanking the cloned insert, and it was used to generate both codingand noncoding-strand cRNA probes used for RNase mapping.Wild-type (AGGGACTTTCC) and mutant (ACTCACTT TCC) NFKB-binding sequences from the human immunodeficiency virus type 1 (HIV-1) long terminal repeat (LTR) (32), cloned into plasmid pGEM, were kindly provided by G. Nabel for cotransfection-competition studies.Cell lines and DNA transfections....

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“…In secondary amyloidosis SAA1 comprises the majority of the amyloid deposition. There are three isoforms of serum amyloid A1 (SAA1 α, SAA1 β, and SAA1 γ) [11,12,13,14,15]. During the inflammation, as in FMF attacks, IL-6 induces hepatic transcription of SAA mRNA and production of SAA increases about 1,000-fold.…”

Section: Introductionmentioning

confidence: 99%

Genetic Risk Factors of Amyloidogenesis in Familial Mediterranean Fever

et al. 2005

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Background/Aims: Evaluation of the risk factors, and phenotype-genotype correlation of familial Mediterranean fever (FMF) gene (MEFV) and serum amyloid A1 (SAA1) gene polymorphisms in renal amyloidosis. Methods: We investigated MEFV and SAA1 genotypes (α, β, and γ isoforms) in 50 FMF patients and 50 healthy children. Tel-Hashomer criteria were used for the diagnosis and severity scoring of FMF. Results: The most common MEFV mutation and SAA1 genotype were M694V/M694V (n = 26/50) and SAA1 α/α (n = 26/50), respectively. Positive family history for amyloidosis was significantly higher (p < 0.001) with more severe clinical course (p = 0.006) in the amyloidosis group than the non-amyloid group. In M694V/M694V mutation, erysipelas-like skin erythema (p = 0.029), arthritis (p = 0.004), arthralgia (p < 0.001) were significantly more frequent with higher severity scores (p = 0.008) than the patients with other mutations. Comparison of the SAA1 α/α genotype with other genotypes revealed more frequent arthritis (p = 0.003) in the SAA1 α/α genotype. In amyloidosis group patients having both M694V/M694V and SAA1 α/α genotypes were the largest subgroup (n = 14, p < 0.001). Logistic regression analysis for amyloidosis corrected risk revealed a 1.2 times increase in M694V/M694V, a 2.4 times increase in SAA1 α/α genotypes and a 2.5 times increase when both are together. Conclusion: Positive family history for amyloidosis and presence of SAA1 α/α genotype in M694V/M694V mutation may predispose to amyloidosis by increasing the clinical severity. Therefore, in such children early colchicine treatment might be recommended even if they are asymptomatic.

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Localization of human SAA gene(s) to chromosome 11 and detection of DNA polymorphisms

Cited by 49 publications

References 20 publications

Serum amyloid A – a review

Serum amyloid A – a review

Identification of cis-acting sequences responsible for phorbol ester induction of human serum amyloid A gene expression via a nuclear factor kappaB-like transcription factor.

Genetic Risk Factors of Amyloidogenesis in Familial Mediterranean Fever

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